New understanding of the aging brain

Variations of the gene that protects the brain as it ages may also indicate a susceptibility for Alzheimer's.

A team of researchers led by scientists at The Hospital for Sick Children (SickKids) has discovered that the mammalian gene, p73 is essential for protecting the brain through the normal aging process. The findings suggest that reduced levels of p73 may increase a person's likelihood of developing Alzheimer's or another neurodegenerative disorder. Their findings are published in the September 2008 issue of Neuron .

Using mouse models, researchers determined that a genetic variation that causes insufficiency for p73 leads to behavioural and anatomical changes commonly observed in the aging brain. Decreased levels of p73 were also found to cause key hallmarks of Alzheimer's disease, namely the appearance of deposits that resemble tangles, which are thought to interfere with and impair thinking and memory.

“These findings are particularly exciting because little is known about why and how the brain ages or develops a disease like Alzheimer's,” says Dr. David Kaplan, Senior Scientist in the Cell Biology Program at SickKids, professor in the Department of Molecular Genetics, at the University of Toronto, Canada Research Chair in Cancer and Neuroscience, and a co-lead author of the study.

“By showing the previously unsuspected role that p73 plays in neurodegeneration, we are one step closer to unraveling this mystery,” adds Dr. Freda Miller, Senior Scientist in the Developmental & Stem Cell Biology Program at SickKids, professor in the Department of Molecular Genetics at the University of Toronto, Canada Research Chair in Developmental Biology, Howard Hughes Medical Institute International Research Scholar and the study's other co-lead author.

These findings could eventually lead to the development of genetic tests that measure levels of the gene and help determine whether a person is at enhanced risk for developing Alzheimer's. Early detection of this genetic anomaly in children could lead to therapies to address the issue before it manifests itself later in life. Other possibilities could include the development of drugs that increase the levels of p73, potentially helping to delay or halt the progression of neurodegenerative disease and aging.

The Alzheimer's Society of Canada estimates that 450,000 (or one in 13) Canadians over the age of 65 have Alzheimer's or similar degenerative brain diseases. Approximately $5.5 billion (CAD) a year is spent on persons with Alzheimer's and related dementias.

The study was supported by the Canadian Institute of Health Research, the Heart & Stroke Foundation, Neuroscience Canada , and SickKids Foundation.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.